title: Analysis of pharmaceutical impurities using multi-heartcutting 2D LC coupled with UV-charged aerosol MS detection.
abstract: To overcome challenges in HPLC impurity analysis of pharmaceuticals, we developed an automated online multi-heartcutting 2D HPLC system with hyphenated UV-charged aerosol MS detection. The first dimension has a primary column and the second dimension has six orthogonal columns to enhance flexibility and selectivity. The two dimensions were interfaced by a pair of switching valves equipped with six trapping loops that allow multi-heartcutting of peaks of interest in the first dimension and also allow "peak parking." The hyphenated UV-charged aerosol MS detection provides comprehensive detection for compounds with and without UV chromophores, organics, and inorganics. It also provides structural information for impurity identification. A hidden degradation product that co-eluted with the drug main peak was revealed by RP × RP separation and thus enabled the stability-indicating method development. A poorly retained polar component with no UV chromophores was analyzed by RP × hydrophilic interaction liquid chromatography separation with charged aerosol detection. Furthermore, using this system, the structures of low-level impurities separated by a method using nonvolatile phosphate buffer were identified and tracked by MS in the second dimension.
authors.affiliation: Small Molecule Pharmaceutical Sciences, Genentech, South San Francisco, CA, USA.
authors.forename: Kelly
authors.initials: K
authors.lastname: Zhang
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.forename: Midco
authors.initials: M
authors.lastname: Tsang
authors.forename: Nik P
authors.initials: NP
authors.lastname: Chetwyn
mesh_terms: D000336:Aerosols / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid / Q000295:instrumentation; D004340:Drug Contamination; D013058:Mass Spectrometry / Q000295:instrumentation; D004364:Pharmaceutical Preparations / Q000032:analysis*; D014466:Ultraviolet Rays
chemical_list: D000336:Aerosols; D004364:Pharmaceutical Preparations
keywords: 2D LC; Charged aerosol detection; Hydrophilic interaction liquid chromatography; Hyphenation; Pharmaceutical analysis